Value of gingival crevicular fluid TREM-1, PGLYRP1, and IL-1ß levels during menopause.

OBJECTIVE: This study aimed to investigate the association of GCF TREM-1, PGLYRP1, and IL-1ß levels with periodontal health in pre- and postmenopausal women. BACKGROUND: Triggering receptor expressed on myeloid cells 1 (TREM-1), activated through its ligand peptidoglycan recognition protein 1 (PGLYRP1), stimulates proinflammatory cytokine production, such as interleukin (IL)-1ß, during periodontal inflammation. Postmenopausal changes may modulate these immune-inflammatory functions. No clinical study has yet investigated the effect of menopause on TREM-1, PGLYRP1, and IL-1ß levels in gingival crevicular fluid (GCF). METHODS: This cross-sectional study included 148 women (age range = 35-65 years), divided into postmenopausal women (PMW) (n = 76, mean age = 54 ± 5 years) and regularly menstruating premenopausal women (RMPW) (n = 72, mean age = 40 ± 4 years). Clinical periodontal parameters were recorded. TREM-1, PGLYRP1, and IL-1ß levels were quantified with enzyme-linked immunosorbent assays. Pearson's Chi-squared test and Mann-Whitney-U test were used to compare categorical and numerical variables, respectively. Spearman's Rho correlation analysis was used to test the linear relationship between variables. Analyte level data were categorized based on the periodontal diagnosis and menopause status (2 × 2 nonparametric factorial ANOVA). RESULTS: No significant differences in TREM-1, PGLYRP1, and IL-1ß levels between PMW and RMPW were observed (p > .05). Mean values of periodontal indexes including probing depth did not differ significantly between PMW and RMPW groups (p = .474). TREM-1 levels were significantly higher in both PMW and RMPW with periodontitis, compared to gingivitis or health (p = .0021). CONCLUSION: Menopause-related changes have no observable effect on GCF levels of TREM-1, PGLYRP1, and IL-1ß. Higher GCF TREM-1 levels in women with periodontitis regardless of their menopausal status indicate that TREM-1 may be an indicator for periodontitis both in premenopausal and postmenopausal women.

Fluvastatin alleviates doxorubicin-induced cardiac and renal toxicity in rats via regulation of oxidative stress, inflammation, and apoptosis associated genes expressions.

Doxorubicin (DOXO) is a cytostatic agent used in the chemotherapy protocol of several cancers for more than 40 years, but usage of this drug in cancer treatment has been limited due to severe renal and cardiac tissue toxicities that may result in death in patients. Fluvastatin (FV) is a fully synthetic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor used as a cholesterol-lowering agent in patients with hypercholesterolemia. Previous studies revealed that FV also exhibits antioxidant, anti-inflammatory, and antitumor activity. Additionally, our previous study indicated that FV exerts a prophylactic effect on DOXO-induced testicular toxicity by preventing lipid peroxidation, supporting the antioxidant system, and regulating the blood-testis barrier-associated genes expression. Herein, we purposed to evaluate the possible therapeutic and the protective effects of FV on the DOXO-induced cardiac and renal toxicitiy model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction (real-time PCR) analyses. Results point out protective use of FV exerts a beneficial effect by repressing lipid peroxidation and by regulating the inducible nitric oxide synthase (iNOS), nitric oxide synthase endothelial (eNOS), nuclear factor kappa-B (NF-κB), and Caspase-3 (Casp3) protein and mRNA expressions, which play an important role in mediating DOXO-induced renal and cardiac toxicity mechanisms. In conclusion, FV may be a candidate agent for the prevention of renal and cardiac toxicities in cancer patients receiving DOXO chemotherapy.

Gingival crevicular fluid galectin-3 and interleukin-1 beta levels in stage 3 periodontitis with grade B and C.

OBJECTIVES: This study aims to evaluate GCF Galectin-3 and Interleukin-1 beta (IL-ß) levels in different grades (B and C) of stage 3 periodontitis, concurrently, and also to investigate their discriminative efficiencies in periodontal diseases. MATERIALS AND METHODS: A total of 80 systemically healthy and non-smoker individuals, 20 stage 3 grade C (S3GC) periodontitis 20 stage 3 grade B (S3GB) periodontitis, 20 gingivitis, and 20 periodontally healthy were enrolled. Clinical periodontal parameters were recorded and GCF Galectin-3 and IL-1ß total amounts were measured by ELISA. Receiver operating characteristics curve was used for estimating the area under the curve (AUC). RESULTS: Galectin-3 and IL-1ß were detected in all participants. Both periodontitis groups had significantly higher GCF Galectin-3 total amounts than periodontally healthy controls (p <0.05). S3GC periodontitis group had also significantly higher GCF Galectin-3 levels than gingivitis group (p <0.05). GCF IL-1ß levels in periodontitis groups were higher than gingivitis and periodontally healthy groups (p <0.05). Galectin-3 exhibited an AUC value of 0.89 with 95% sensitivity to discriminate S3GC periodontitis from periodontal health, an AUC value of 0.87 with 80% sensitivity to discriminate S3GC periodontitis versus gingivitis, while an AUC value of 0.85 with 95% sensitivity to discriminate S3GB periodontitis from healthy controls. CONCLUSIONS: GCF Galectin-3 levels are involved in the pathogenesis of periodontal diseases. Galectin-3 showed excellent diagnostic performances to discriminate S3GB and S3GC periodontitis from periodontal health and gingivitis. CLINICAL RELEVANCE: The present findings suggest that GCF Galectin-3 levels may be useful in the diagnosis of the periodontal diseases.

The solubility, pH value, chemical structure, radiopacity, and cytotoxicity of four different root canal sealers: an in vitro study.

OBJECTIVE: The aim of this study was to investigate solubility, pH value, chemical structure, radiopacity, and cytotoxicity of AH Plus BC, TotalFill BC, AH Plus, and AH Plus Jet sealers. MATERIALS AND METHODS: Cytotoxicity analysis with direct and extraction tests at 3 different concentrations (1:1, 1:2, 1:4 v/v%) and time (24 h, 48 h, and 72 h) on Saos-2, PdLF, and THP-1 cell lines, chemical structure with scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) analysis, solubility, pH, and radiopacity values of AH Plus BC, TotalFill BC, AH Plus, and AH Plus Jet were evaluated. For statistical analyses of the groups, repeated measures, factorial, and one-way ANOVA tests were used. The statistical significance level was set at p < .05. RESULTS: Resin-based sealers showed higher cytotoxicity values than the bioceramic-based sealers (p < 0.05). Time and concentrations were effective on the cell viabilities for cell lines. Higher peaks of calcium were detected bioceramic-based sealers and higher amount of zirconium was detected in AH Plus BC (p < 0.05). AH Plus BC showed similar radiopacity value with AH Plus, AH Plus Jet, whereas TotalFill BC showed the lowest radiopacity (p < 0.05). Bioceramic-based sealers had higher pH values in all experiment periods, and the difference between resin- and bioceramic-based sealer groups was significant (p < 0.05). However, the solubility values of the tested root canal sealers revealed no differences (p > 0.05). CONCLUSIONS: The newly produced AH Plus BC Sealer showed similar properties with TotalFill BC, and their biological properties were better than AH Plus and AH Plus Jet. CLINICAL RELEVANCE: AH Plus BC could be a possible alternative to other bioceramic- or resin-based sealers.

The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS).

BACKGROUND: Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS. METHODS AND RESULTS: Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05). CONCLUSIONS: In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.

The trefoil factor family 1 (TFF-1) and 3 (TFF-3) are upregulated in the saliva, gingival crevicular fluid and serum of periodontitis patients.

OBJECTIVE: This study aimed to investigate the levels of trefoil factor family (TFF)-1, TFF-3 and interleukin (IL)-1ß in gingival crevicular fluid (GCF), saliva and serum of patients with gingivitis, stage 3 periodontitis and healthy individuals. MATERIALS AND METHODS: A total of 100 individuals consisting of 25 periodontally healthy, 25 gingivitis and 50 stage 3 periodontitis, were enrolled in the study. Clinical periodontal examinations were recorded and GCF, saliva and serum samples were obtained. TFF-1, TFF-3 and IL-1ß were measured by ELISA. RESULTS: TFF-1 and TFF-3 levels in both GCF, saliva and serum were higher in periodontitis patients than healthy controls (p < .001) and gingivitis group (p < .01). The levels of these peptides in all biofluids were similar between gingivitis and healthy control groups (p > .05). GCF, saliva and serum IL-1ß levels were also higher in periodontitis patients than the controls (p < .01). Periodontitis patients had elevated GCF and saliva IL-ß levels than gingivitis group (p < .001). CONCLUSION: Elevated TFF-1 and TFF-3 levels both locally and systemically in periodontitis in parallel to increased IL-1ß levels might suggest that these peptides are involved in host response during the periodontal tissue destruction.

May ganglion cell complex analysis be a marker for glaucoma susceptibility in unilateral Fuchs' uveitis syndrome?

PURPOSE: To compare retinal nerve fiber layer (RNFL) thickness and ganglion cell-inner plexiform layer thickness (GCIPLT) in the affected eyes to fellow unaffected eyes of patients with unilateral Fuchs' uveitis syndrome (FUS) and analyze their change over time. METHODS: Twenty seven unilateral FUS patients who did not have concomitant systemic or ocular disease were retrospectively enrolled. Central macular thickness (CMT), RNFL thickness, and GCIPLT measurements were evaluated. Data was analyzed using the non-parametric Brunner-Langer model (LD-F2 design) and Wilcoxon signed-rank test. RESULTS: The mean age of the patients was 40.2 ± 10.2 years. The median disease duration was 11 (2-62) months. The median best-corrected visual acuity (BCVA) of the affected eyes and the fellow eyes was 0.22 (0.00-2.50) vs. 0.00 (0.0-0.10) logMAR at the initial visit and 0.05 (0.00-2.50) vs. 0.00 (0.0-0.30) logMAR at the final visit. The change in BCVA was found significant in the affected eyes, but not in the fellow eyes (p < 0.001 and p = 0.287, respectively). The median CMT in the affected eyes at the final visit was not statistically different from the value at the initial visit (255 (157-306) vs. 245 (140-310) µm, p = 0.256). The change in RNFL thickness over time in the affected eyes was similar to the fellow unaffected eyes of the patients with unilateral FUS at all quadrants, with non-significant time and group effects (p > 0.05). However, median GCIPLT in all quadrants (except superonasal) in the affected eyes was statistically lower than the fellow eyes at the initial and final visits (p < 0.05). The most affected quadrant of the ganglion cell complex was inferonasal in the involved eyes (79 (42-97) vs. 75 (43-87) µm) at initial and final visits (p = 0.033 for time effect and p < 0.001 for group effect, respectively). CONCLUSION: Median CMT and RNFL thickness did not change during follow-up in the affected eyes of patients with unilateral FUS. Median GCIPLT in the affected eyes declined over time in all quadrants. Ganglion cell loss was also most prominent in the inferonasal quadrant in the affected eyes. FUS patients should be followed up long-term in terms of ganglion cell loss, especially in the inferonasal quadrant.

Oral health and emotional well-being in premenopausal and postmenopausal women: a cross-sectional cohort study.

BACKGROUND: Menopause, the absence of ovarian sex steroids, is frequently accompanied by emotional and physiological changes in a woman´s body, as well as oral health changes. The present study aimed to evaluate the association between the periodontal health status and emotional and physical well-being among postmenopausal women (PMW) in comparison with regularly menstruating premenopausal women (RMPW). METHODS: A total of 115 women (PMW, n = 56, mean age ± SD: 54 ± 5; RMPW, n = 59, mean age ± SD: 41 ± 4) received a comprehensive medical assessment and a full-mouth oral examination. All completed the Women's Health Questionnaire (WHQ) to measure emotional and physical well-being. The corresponding bone mineral density (BMD) scores were obtained from participants´ medical records. RESULTS: Tooth loss was significantly higher in PMW than RMPW after adjusting for age (3.88 ± 2.41 vs 2.14 ± 2.43, p < 0.05). No significant difference was found in the prevalence of periodontitis between the two groups (PMW: 39.2%, RMPW: 32.2%, p > 0.05). The prevalence of periodontitis was associated with fewer daily brushing sessions in PMW (p = 0.021). Based on the WHQ, both PMW and RMPW with periodontitis had higher ''depressed mood'' scores compared to periodontally healthy women (p = 0.06 and p = 0.038, respectively). The women who reported fewer daily toothbrushing sessions found to have higher depressive mood scores (p = 0.043). CONCLUSIONS: Presence of periodontitis is associated with the emotional and physical well-being of women and reinforcement of oral healtcare is recommended at different stages of a woman's life including menopause to reduce the risk for early tooth loss in women.

Local and systemic levels of aMMP-8 in gingivitis and stage 3 grade C periodontitis.

THE OBJECTIVE: This study aimed to analyze active matrix metalloproteinase (aMMP-8) levels in gingival crevicular fluid (GCF), saliva and serum in the context of new criteria of gingivitis and stage 3 grade C periodontitis. THE BACKGROUND: Periodontal disease is an inflammatory process that can result in tooth loss and also is considered a modifying factor for systemic health. Matrix metalloproteinase (MMP)-8 is the major collagenase of periodontal tissue breakdown. METHODS: Totally 83 systemically healthy and non-smoker individuals consisting of 23 periodontally healthy, 20 gingivitis and 40 stage 3 periodontitis, were recruited to the study. Clinical periodontal examinations of probing depth (PD), clinical attachment loss (CAL), gingival index (GI), plaque index (PI) and bleeding on probing (BOP) were recorded; and GCF, saliva and serum samples were obtained. aMMP-8 was measured by immunofluorometric assay (IFMA). RESULTS: GCF and serum aMMP-8 levels were significantly increased in periodontitis and gingivitis compared to healthy ones (P < .001), whereas gingivitis and periodontitis patients showed similar levels of aMMP-8 in GCF and serum (P > .05). Saliva levels of aMMP-8 were higher in periodontitis patients than both gingivitis and healthy individuals (P < .001). There was no significant difference in salivary aMMP-8 levels between gingivitis group and healthy controls (P > .05). CONCLUSION: These findings support the involvement of aMMP-8 in periodontal diseases and suggest that its local and systemic levels can reflect stage 3 grade C periodontitis. Moreover, aMMP-8 in GCF and serum seems to have a potential to differentiate between gingivitis and periodontal health.

Carbapenem-resistant Klebsiella pneumonia infection outbreak in a tertiary urology clinic: analysis of influencing factors with a controlled trial

Background/aim: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections encountered in urology patients differentiate from infections caused by other factors, both in respect to prophylaxis and treatment stage, and require a special approach. We aimed to analyse the predisposing factors and the antibiotherapies for CR-KP infection outbreak in a tertiary urology clinic. Materials and methods: There were 75 patients in the CR-KP positive group (Group I) and 146 patients in the CR-KP negative group (Group II). Analysis of the predisposing factors for CR-KP infection and comparison of the reinfection rate and the antibiotherapies in the 2 groups were the endpoints. Results: In the first group, age, comorbidity, previous antibiotic use, and nephrostomy tube rates were higher (P = 0.015, P = 0.001, P = 0.004, and P < 0.001, respectively). In the second group, open urological surgery rate, and the proportion of patients presenting with flank pain, lower urinary tract symptoms, and haematuria were higher (P = 0.029, P < 0.001, P < 0.001, and P = 0.007). In the first group, the proportion of patients treated with transurethral bladder tumour resection was higher, whereas, percutaneous nephrolithotomy was higher in the second group (P = 0.045 for both). While hospitalization and Foley catheterization duration were longer in the first group (P < 0.001 for both), double J stent and nephrostomy duration were longer in the second group (P < 0.001 and P = 0.005). Mean leukocyte count at admission was higher in the first group (P < 0.001). Conclusion: Advanced age, comorbidities, previous antibiotic use, and prolonged Foley catheterization duration are predisposing factors for this infection in the urology department. Two-week administration of combination antibiotic regimens containing carbapenem were effective for the treatment of this infection.

Deletions in SERPING1 Lead to Lower C1 Inhibitor Function: Lower C1 Inhibitor Function Can Predict Disease Severity.

BACKGROUND: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. METHODS: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. RESULTS: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0-18.7; 5.8%, 0-16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11-78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = -0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = -0.404, p = 0.001) and more frequent annual attacks (r = -0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. CONCLUSION: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.

The improvement of biocompatibility of adhesives : The effects of resveratrol on biocompatibility and dentin micro-tensile bond strengths of self-etch adhesives.

OBJECTIVE: The aim of this in vitro study is to evaluate the effects of resveratrol (RES) addition on the cytotoxicity and microtensile bond strength (µTBS) of different adhesives. MATERIALS AND METHODS: Five self-etching adhesives (G-aenial Bond-GC, Optibond All in One-Kerr, Gluma Self Etch-Kulzer, Clearfil S3 Bond-Kuraray, and Nova Compo-B Plus-Imicryl) were tested. They were applied to L-929 cell culture by the extract method. In the test groups, 0.5 µM RES (Sigma-Aldrich) was added into the medium. Cell viability was assessed by MTT assay after 24 h. Human extracted third molars were used for µTBS test (n = 7). The adhesives with or without 0.5 µM RES addition were applied on dentin surfaces. A composite build-up was constructed. Then, the specimens were sectioned into multiple beams with the non-trimming version of the microtensile test and subjected to microtensile forces. Statistical analysis was performed using ANOVA and post hoc Tukey test (p Ë‚ 0.05). RESULTS: The extracts of all adhesives decreased the cell viability. However, RES addition increased the cell viability in all groups (p Ë‚ 0.05). RES addition did not cause any decrease in µTBS values of the adhesives compared to baseline. Optibond All in One showed the highest µTBS after RES addition. It was followed by Clerafil S3 Bond and Nova Compo-B Plus. No difference was determined between the Optibond All in One and Clearfil S3 Bond. There was difference between Optibond All in One and Nova Compo-B Plus (p Ë‚ 0.05). CONCLUSION: RES addition may improve the biocompatibility without causing negative influence on µTBS of the adhesives. CLINICAL RELEVANCE: RES addition has clinical applicable potential to overcome the adverse biocompatibility of adhesives.

Effect of orthodontic force magnitude on cytokine networks in gingival crevicular fluid: a longitudinal randomized split-mouth study.

OBJECTIVE: To compare effect of two different orthodontic forces on maxillary canine distalization via evaluation of 30 analytes including cytokines, growth factors, and chemokines in gingival crevicular fluid (GCF) obtained from tension and compression sites. DESIGN: Longitudinal, split-mouth, randomized controlled trial. METHODS: The upper right and left canines were randomly distalized by a continuous force of either 75 or 150 g, in 15 individuals with Class II division 1 malocclusion. GCF samples were obtained from the tension and the pressure sides of each canine at appliance placement (baseline) and after force application at 24 hours and 28 days without reactivation of the coil spring. The protein content of GCF was analysed by a multiplexed immunoassay. The effects of force, side, and time on the analyte levels were assessed by the Brunner-Langer method. OUTCOME: The changes of GCF analyte levels from baseline to 24 hours and 28 days. RANDOMIZATION: Coin flipping was used for allocation of two forces. BLINDING: The participants and periodontist who performed clinical measurements and GCF sampling were blinded to group assignment and interventions (double-blinded trial). RESULTS: All patients completed the study. No harm was observed. When compared to baseline, both forces caused significant up-regulation of tumour necrosis factor-α and interleukin (IL)-1RA in the tension and the pressure sides at 28 days (P < 0.05), but not at 24 hours. Although GCF volume was similar between the two force groups over time (P > 0.05), IL-8 and MCP-1 levels in GCF were significantly lower at the pressure sites receiving higher force (150 g) at 24 hours (P < 0.05). LIMITATIONS: Although sample size (15 patients, 30 teeth) was adequate according to the initial power calculation, borderline significances may indicate lack of power or large variability among the samples. CONCLUSIONS: Although a higher force of 150 g did not result in increased cumulative canine movement or GCF production, selective host mediators were differentially regulated by the magnitude and duration of the force. REGISTRATION AND TRIAL PROTOCOL: The trial was registered retrospectively in the U.S. National Institutes of Health Clinical Trials Registry. Full details of trial protocol NCT03555747 are available on request.

Mid-dose losartan mitigates diabetes-induced hepatic damage by regulating iNOS, eNOS, VEGF, and NF-κB expressions

Background/aim: Losartan, an antihypertensive drug, is highly preferred in patients with diabetes mellitus (DM) and hypertension because of its retarding effect on diabetic nephropathy. In this study, we investigated the potential therapeutic effect of different doses of losartan on hepatic damage in a streptozotocin (STZ, 50 mg/kg)-induced DM model in rats. Materials and methods: In this study, five different groups were formed: control, DM, low-dose losartan (5 mg/kg), mid-dose losartan (20 mg/kg), and high-dose losartan (80 mg/kg). Liver tissues of experimental groups were evaluated immunohistochemically for TUNEL, iNOS, eNOS, VEGF, and NF-κB pathways. In addition to immunohistochemical analysis, analyses of SOD and MDA, which are oxidative stress markers, were also performed and the results were evaluated together. Results: When biochemical and immunohistochemical findings were evaluated together, it was found that the results obtained from the mid-dose losartan group were closer to those of the control than the other groups. Conclusion: This study indicated that mid-dose losartan administration may have a therapeutic effect by inhibiting apoptosis and regulating iNOS, eNOS, VEGF, and NF-κB protein expressions in DM-induced hepatic damage.

Pretreatment with paricalcitol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischemia-reperfusion injury
.

BACKGROUND: Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). The inflammatory response that drives IRI involves upregulation of matrix metalloproteinases (MMPs), which results in proteolytic degradation of renal microvascular matrix. Evidence suggests a potential protective role of active vitamin D on ischemic injury by downregulating MMPs. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal IRI model and the potential beneficial effect of paricalcitol on both level and expression of MMPs and tubular injury caused by IRI. MATERIALS AND METHODS: 20 Wistar albino rats were divided into three groups: sham-operated, ischemia-reperfusion, and paricalcitol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 minutes followed by 24 hours of reperfusion. The analysis of serum creatinine and levels of MMPs were performed after 24 hours of IRI. The effects of paricalcitol on the quantity and expression of MMP-2 and MMP-9 in renal tubular epithelial cells were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS: Creatinine levels decreased in the paricalcitol group, although this was not proven to be significant. Rats in the paricalcitol group showed significant decrease in both level and expression of MMPs and in tubular injury scores as compared to the IRI group. CONCLUSION: Paricalcitol may attenuate renal tubular injury caused by IRI by decreasing both level and expression of MMPs. Further studies are required to investigate the interplay between activated vitamin D and MMPs in AKI.
.

Pretreatment with nebivolol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischaemia-reperfusion injury.

AIM: Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischaemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischaemia-reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a ß1 -adrenergic receptor blocker, on both MMP-2 and -9 level and expression and tubular injury caused by IRI. METHODS: Twenty Wistar albino rats were divided into three groups: sham-operated , ischaemia-reperfusion, and nebivolol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 min followed by 24 h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24 h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS: Creatinine levels increased significantly in the ischaemia-reperfusion group compared to the sham-operated group. Rats in the nebivolol-pretreated group showed significant decrease in expression and quantity of MMP-2 and MMP-9 during IRI. The pathological examinations demonstrated significantly low level of tubular injury score in nebivolol-pretreated group. CONCLUSION: Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.

The effects of chemoradiotherapy on recurrence and survival in locally advanced rectal cancers with curative total mesorectal excision: a prospective, nonrandomized study.

BACKGROUND: There are only two prospective, randomized studies comparing preoperative long-term chemoradiotherapy and postoperative chemoradiotherapy in locally advanced rectal cancer (LARC); however, conflicting results in terms of locoregional recurrence (LR) and survival rates have been reported. This prospective study aims to compare the effects of preoperative versus postoperative chemoradiotherapy on recurrence and survival rates in LARC patients. METHODS: From January 2003 to January 2016, a total of 336 eligible patients who were clinically diagnosed with LARC (T3-T4 tm or node-positive disease) were prospectively assigned into preoperative chemoradiotherapy (n = 177) and postoperative chemoradiotherapy (n = 159) groups. The preoperative treatment consisted of 50.4 Gy total dose of radiotherapy (delivered in fractions of 1.8 Gy) and concomitant two cycles chemotherapy of 5-fluorouracil and leucovorin. The patients in the preoperative group underwent curative total mesorectal excision (TME) following long-term chemoradiotherapy. Surgery was performed 8 (range 4-12) median weeks after the completion of the chemoradiotherapy. Similar protocol was administered to the postoperative group 4 weeks after the operation. Four cycles of adjuvant chemotherapy were added to the groups. The primary end points were locoregional recurrences and 5-year cancer-specific, overall, and disease-free survivals. RESULTS: The mean follow-up period was 60.4 (range 12 to 168) months. Five-year cumulative incidence of locoregional recurrence (LR) was 7.4% in the preoperative group and 13.4% in the postoperative group (p = 0.021). Five-year cancer-specific survival (CSS) was 87.5% in the preoperative group and 80% in the postoperative group (p = 0.022). Overall survival (OS) was 79.8 versus 74.7% (p = 0.064), disease-free survival (DFS) was 75.2 versus 64.8% (p = 0.062), and severe late toxicity was 7.4 versus 13.2% (p = 0.002), respectively. The rate of patient compliance was higher in the preoperative group (p < 0.001). CONCLUSIONS: Preoperative chemoradiotherapy, as compared with postoperative chemoradiotherapy, significantly improved local control, patient compliance, CSS, and late toxicity and suggested a trend toward improved overall and disease-free survival.

Efficacy of simvastatin in reducing postoperative adhesions after thyroidectomy: an experimental study.

BACKGROUND: We aimed to investigate whether simvastatin had any impact on the prevention of adhesion formation after thyroidectomy in a rat model. METHODS: This study was performed in 66 Wistar albino rats randomized into three experimental groups. A right hemithyroidectomy was carried out in all the rats. Simvastatin was administered locally at a dose of 0.5 mg/kg and 0.8 mg/kg. Control rats received a saline solution only. Changes during the 1st week, 1st month and 3rd month were evaluated. Efficacy of the treatment was assessed by using a scoring system. RESULTS: The severity of adhesions in low-dose simvastatin group was significantly less than the control and high-dose groups during the 1st and 3rd month (p < .05). In addition, adhesions were less in the high dose group during the 3rd month, when compared to the control group (p < .05). Moreover, fibrosis and fibroblast scores, which represent adhesions, were significantly lower in low-dose and high-dose groups at 3rd month, compared to controls (p < .05). CONCLUSIONS: We investigated the influence of simvastatin application on post-thyroidectomy adhesion formation in rats. Whether adhesions, causing technical difficulties during neck redo surgery, can be reduced by the use of simvastatin in human, needs to be studied.

Acetazolamide in vestibular migraine prophylaxis: a retrospective study.

The aim of this study is to check the efficacy of acetazolamide in the prophylaxis of vestibular migraine (VM). Treatment options in VM are mainly based on migraine guidelines. We tried to assess the efficacy of acetazolamide in these patients depending on clinical similarities with episodic ataxia type 2 and familial hemiplegic migraine responding to the drug. This is a retrospective cohort study. Among 50 patients with VM and prescribed acetazolamide 500 mg/day, 39 patients were studied as five had been lost on follow-up and six had stopped taking the drug due to side effects. Vertigo and headache frequency determined by number of attacks per month, and the severity determined by visual analog scales measured in centimeters from 0 to 10 were collected from the records. Initial reported figures for frequency and severity were compared with the results gathered after 3 months of treatment. The results were compared. Acetazolamide was effective in reducing both the frequency and severity of vertigo and headache attacks and this effect was more prominent for vertigo frequency and severity.

Duplex ultrasonography findings are not related to menstrual cycle phases in women with early symptoms of lower extremity chronic venous disease.

PURPOSE: To investigate if duplex ultrasonography findings change according to the menstrual cycle phases in women with early symptoms of lower extremity chronic venous disease. METHODS: Thirty women (60 extremities) aged 18-50 years with regular menstrual cycles who presented with complaints of telangiectasia and/or trunk varices with accompanying leg pain were evaluated prospectively by duplex ultrasonography at three different times of a single menstrual cycle. Previous DVT or menstrual irregularities were exclusion criteria. All exams were performed by the same radiologist, under the same conditions. Reflux was provoked in the deep veins, great saphenous vein (GSV), and small saphenous vein (SSV) using the Valsalva maneuver. Reflux times in each vein and average diameters of the GSV and SSV were recorded. RESULTS: Reflux times showed no significant differences in any of the vein segments and the diameters of GSV and SSV were similar in the different menstrual phases (p > 0.05). Reflux was not predominant at any specific phase, and its presence was independent of menstrual phase. CONCLUSIONS: Reflux was not specific to a particular phase of menstrual cycle in women with early symptoms of chronic venous disease.